Rate Of Chromosomal Abnormalities Research Articles

Large Intra-Age Group Variation in Chromosome Abnormalities in Human Blastocysts

Research Question: Is maternal age only a gross predictor of chromosome abnormalities in human embryos? Design: Here, we evaluated the less-studied variation in chromosome abnormality rates in embryos of patients within the same age group. Patients undergoing IVF and PGD for chromosomal abnormalities in ~127 different IVF clinics were included. PGT-A analysis was performed by a single reference laboratory using array CGH or NGS. To get an estimate of the range of abnormalities observed, the aCGH and NGS data were studied both independently and together. Results: The overall results showed the typical increase in aneuploidy rates with advancing maternal age (AMA) but extensive variability within each age group. Conclusions: Increasing aneuploidy with maternal age has been demonstrated in live births, unborn fetuses, IVF embryos and oocytes. In contrast, post-meiotic and other abnormalities that might lead to mosaicism, polyploidy and haploidy, are commonplace (around 30%), regardless of maternal age. Here we conclude that age is only a gross predictor of chromosome abnormalities in IVF embryos. In contrast to the existing standard of offering PGT-A to AMA patients, the high rate and extreme variation of chromosomal abnormalities in human embryos may warrant PGT-A for further IVF cycles even in younger age groups, especially if a history of increased levels of aneuploidy is evident. Furthermore, better indicators are needed to determine which patients are at a higher risk of producing increased levels of aneuploid embryos.

Prenatal and neonatal outcomes of pregnancies diagnosed with fetal single umbilical artery

Objective To investigate the associated anomalies and outcomes of fetuses diagnosed as having a single umbilical artery (SUA) which were reported inconsistently in previous studies. Methods The data of 82 pregnancies with fetal SUA, 35 of which were complex, and 47 isolated SUA (iSUA) and 100 pregnancies with fetal double umbilical arteries (DUA) between June 2018 and July 2020 were retrieved. We compared the maternal characteristics, and pregnancy and fetal outcomes of the three groups (iSUA, SUA, and DUA). Results Of 82 fetuses with SUA, 35 had 64 major structural abnormalities. 20 of these 35 fetuses (57.1%) had cardiovascular malformations, 12 (34.2%) had central nervous, 10 (28.5%) had genitourinary, and eight (22.8%) had gastrointestinal system malformations. Isolated SUA was present in SUA. Compared with the 100 DUA fetuses, SUA was a risk for intrauterine growth restriction (IUGR), preterm delivery, Apgar scores of <7, and admission to the neonatal intensive care unit. Having fetal chromosomal or structural abnormalities, was a risk for amnion fluid abnormality, pregnancy termination, intrauterine fetal death, early neonatal death, and a low live birth ratio in SUA cases. Conclusion SUA has an increased rate of fetal structural and chromosomal abnormalities. Among them, the most detected one is cardiac and the second most common one is central nervous system malformations. Pregnancies with fetal SUA have increased risk for IUGR, preterm delivery, low Apgar scores, and admission to the neonatal intensive care unit. The presence of additional structural or chromosomal malformations increases the rate of these adverse pregnancy risks. Thus, these cases warrant dedicated fetal ultrasonographic organ screening and close prenatal follow-up.

Comprehensive analysis of early pregnancy loss based on cytogenetic findings from a tertiary referral center

BackgroundPregnancy loss is one of the most common complications during pregnancy. Clinical consultation based on etiology analysis are critical for reducing anxiety and distress. This study aimed to perform a comprehensive analysis for products of conception (POC) in miscarriage based on genetic etiology and clinical information.MethodsA retrospective study was conducted according to cytogenetic findings of 1252 POC from spontaneous pregnancy loss over 11 years. The frequencies and profiles of chromosomal abnormalities were discussed according to the classification of women with different maternal ages, previous miscarriage history, normal live birth history, and different modes of conception.ResultsA total of 667 (53.2%) chromosomal abnormalities were observed, including 592 (47.3%) cases of numerical abnormalities, 38 (3.0%) cases of structural abnormalities, and 37 (3.0%) cases of mosaic aberrations. In women above 40 years of age, the rates of chromosomal abnormalities and viable autosomal trisomy were significantly higher than those in women with ≤ 29, 30–34, and 35–39 years of age (p < 0.05). The frequency of abnormal karyotype in women with normal live birth history was 61.1%, significantly higher than 52.5% in women without normal live birth history (p < 0.05). There was no significant differences among women without, with 1–2, and ≥ 3 previous miscarriages regarding the rate of abnormal karyotype (p > 0.05); viable autosomal trisomy was less common in women with ≥ 3 previous miscarriages than women with < 3 miscarriages. The frequency of chromosomal abnormalities was 49.0% and 55.0% in women with assisted conception and natural conception (p > 0.05), respectively; monosomy X was more frequently detected in women with natural conception than assisted conception.ConclusionThe frequencies and profiles of chromosomal abnormalities in early miscarriages are strongly associated with clinical information including maternal age, previous miscarriage, live birth history, and mode of conception. Cytogenetic analysis of POC should be recommended to women with a first miscarriage and women with normal live birth history.

Study on the application of ultrasonography in the diagnosis of fetal cardiac structural abnormalities and the relationship between fetal cardiac structural abnormalities with chromosome abnormalities in early pregnancy.

BackgroundTo explore the significance of multiple ultrasonic soft indexes such as Nuchal translucency (NT) in detection of cardiac structural malformations and chromosome abnormalities in fetal systematic screening in the first trimester, and to understand the value of combined transvaginal ultrasound (TVUS) in congenital heart disease (CHD) screening.MethodsA total of 3,356 pregnant women who underwent early NT screening were screened by systematic ultrasound to monitor and evaluate the sensitivity and specificity of NT, tricuspid valve (TV), ductus venosus (DV) in the diagnosis of fetal CHD. According to the different intervals of NT thickening, the patients were divided into four groups, the detection rates of CHD and abnormal karyotypes in each group were compared, and the consistency of transabdominal and combined transvaginal ultrasonography was compared.ResultsA total of 3,356 cases of early pregnancy were examined by NT. A total of 66 cases of CHD were detected, and the detection rate was 1.97%. Among the 66 CHD cases, 14 cases underwent chromosome karyotype examination and 12 of those cases had abnormal results. With the increase of NT thickness, the detection rates of cardiac structural abnormalities and chromosomal abnormalities all showed a linear increasing trend. The sensitivity of the NT ≥2.5 mm group was as high as 63.64%, and the ductus venosus α wave (DVα) reverse specificity, and the positive likelihood ratio was 99.57% and 53.41%, respectively. The sensitivity of the 3 indicators combined was 66.67%, which was higher than that of any single index, and the area under the receiver operating characteristic (ROC) curve of these 3 indicators combined was the largest (AUC: 0.86). 4. Seventy patients in total were examined by combined TVUS. There is no statistical difference between the two.ConclusionsA positive linear correlation was found between NT thickness and the detection rate of fetal cardiac structural abnormality and chromosome abnormality. Early pregnancy NT screening combined with TV blood flow spectrum and DV blood spectrum screenings has high specificity and sensitivity in the diagnosis of CHD. Combined transabdominal and TVUS in early pregnancy can reduce the rates of misdiagnosis and missed diagnosis of fetal CHD.

Can Culture Media Impact Preimplantation Embryo Aneuploidy?

With continued improvements in blastocyst culture, cell sampling approaches, and genetic analysis platforms, the resulting improvements in embryo development and the resolution and accuracy of chromosome analysis have provided valuable insights into the preimplantation embryo. This includes the impact of in vitro culture conditions on chromosomal dynamics. Specifically, through analysis of embryo aneuploidy and mosaicism, a growing number of reports indicate that rates of chromosomal abnormalities can vary between IVF centers. Because differences in mosaicism reflect mitotic errors, this endpoint analysis suggests that IVF laboratory-controlled variables during embryo development may be influencing chromosome separation and segregation. A growing body of literature suggests that culture media may be one variable influencing preimplantation embryo aneuploidy and mosaicism. However, these data are far from definitive in demonstrating cause-and-effect. Whether reported differences may be due to media formulation, use of sequential media or single-step media, or uninterrupted culture approaches is unknown. Importantly, variables directly impacting media performance and embryo development, including pH, temperature, osmolality, and oxygen concentration, must also be considered and make it difficult to isolate the impact of culture media as the sole factor responsible. These IVF laboratory variables will be reviewed and literature suggesting a possible link to mitotic aneuploidy/mosaicism will be discussed.

Application of expanded noninvasive prenatal test in prenatal diagnosis of fetuses with increased nuchal translucency

Objectives To investigate the efficiency of the upgraded noninvasive prenatal test (NIPT-Plus) in fetuses with increased nuchal translucency (NT). Methods Fetuses with an increased NT at or above 2.5 mm were selected for prenatal diagnosis. Amniotic fluid was collected from all cases for karyotype analysis and copy number variation sequencing (CNV-seq), and cell-free fetal DNA (cfDNA) in maternal blood was tested using Noninvasive Prenatal Test (NIPT-Plus) before amniocentesis in some cases. The results of amniocentesis with different NT thicknesses were analyzed and compared with those of NIPT-Plus. Results A total of 125 eligible patients were divided into group A (2.5 mm ≤ NT < 3.0 mm) and group B (NT ≥ 3.0 mm). In group A, the detection rate of chromosomal aneuploidy and pathogenic copy number variation (CNV) was 10.6% and 6.4%, respectively. The total chromosome abnormality rate in group B (34.7%) was significantly higher than that in group A (17%). In 72 patients who underwent NIPT-Plus and amniocentesis, chromosomal aneuploidy accounted for 80.8% of the total chromosomal abnormalities. Among 21 cases of chromosomal aneuploidy, NIPT-Plus detected 20 cases. The sensitivity and specificity of NIPT-Plus toward aneuploidy detection were 95.2% and 100%, respectively. Among the five cases of pathogenic CNV, only two were detected using NIPT-Plus. Conclusion NIPT-plus is recommended as the first choice for fetal diagnosis in pregnant women with 2.5 mm ≤ NT < 3.0 mm who do not accept invasive prenatal diagnosis. When NT ≥ 3.0 mm and NIPT-Plus detects chromosomal aneuploidy, a rapid prenatal diagnosis can be performed through amniocentesis. In cases where NIPT-Plus yields negative results, amniocentesis still needs to be performed to detect chromosome microdeletions/duplications in order to avoid a missed diagnosis.

Karyotype analysis of amniotic fluid cells and report of chromosomal abnormalities in 15,401 cases of Iranian women

The aim of present study was to assess the karyotypes of amniotic fluid cells and find the frequency of chromosomal abnormalities and their significance in clinical setting. A total of 15,401 pregnant women were assessed from March 2016 to May 2019, and 14,968 amniotic fluid samples were successfully cultured. These fetuses were grouped according to different indications including advanced maternal age, abnormal nuchal translucency (NT) values, positive first/second trimester screening results, high risk NIPT results, very low PAPP-A and free β-hCG multiples of the normal median (MoM) results, abnormal ultrasound findings or previous history of chromosomal abnormalities. Results indicated the presence of normal karyotype in 90.2% (13,497/14,968) of fetuses. Totally, 46.4% (6945/14,968) of fetuses were 46,XX and 43.8% (6552/14,968) had 46,XY chromosome pattern. A total of 1077 abnormal karyotypes were found among 14,968 fetuses, thus the rate of abnormal fetuses was calculated to be 7.2% (1072/14,968). Meanwhile, a total of 394 cases (2.8%) had a normal polymorphism in their karyotype. In other words, abnormal karyotypes were detected in one of 13.9 cases of patients underwent amniocentesis. Down syndrome, Edward’s syndrome, abnormal mosaicisms and Patau’s syndrome were detected in 4.4% (659/14,968), 0.57% (85/14,968), 0.49% (74/14,968) and 0.24% (36/14,968) of cases, respectively. Sex chromosomal abnormalities including Klinefelter syndrome, Turner syndrome and 47,XXX karyotype were detected in 64 cases (0.43%). In this article, the rates of chromosomal abnormalities are compared between different groups of patients based on the advanced maternal age, abnormal NT values, very low PAPP-A and free β-hCG MoMs results, and positive FTS results. The current investigation provides insight into the most appropriate indications for amniocentesis in Iran.

Oocyte Cryopreservation at a Young Age Provides an Effective Strategy for Expanding Fertile Lifespan.

With an upward trend in delaying parenthood, women across the world face an increasing risk of age-related infertility and involuntary childlessness. Elective oocyte banking strategies offer women the possibility to protect part of their reproductive potential until personal finances, personal relationship, or career have stabilized. Timely collection and cryopreservation of oocytes when they are most competent and chromosomal abnormality rates have not yet escalated are crucial for achieving high live births through in vitro fertilization (IVF) treatment at a later stage. To promote reproductive autonomy, women shall be informed about the decrease in fertility rates that sharply intensifies from the age of 35 years and the strategies available to maintain their reproductive potential. Together with this information, women should also recognize the limitations of available strategies including expected live birth rates, costs of the procedures, and overall approach performance, which is mainly associated with age at cryopreservation, number of oocytes banked, and age at accessing the banked oocytes. Evidence-based statistics are not yet available due to the relatively short period in which oocyte cryopreservation has been offered for elective purposes and the scarce number of patients returning for accessing their oocytes. However, to evaluate the applicability of fertility cryopreservation on a large scale, several theoretical models have been proposed to assess the expected efficacy and overall cost-effectiveness of different oocyte banking strategies. In this study, we review current oocyte cryopreservation methodologies, their applications, and outcomes. Moreover, we summarize current evidence regarding known parameters affecting oocyte banking efficacy. Finally, we discuss key points that could play a role in improving access to the service and optimization of oocyte banking frameworks.

Analysis of Genomic Copy Number Variation in Miscarriages During Early and Middle Pregnancy.

The purpose of this study was to explore the copy number variations (CNVs) associated with miscarriage during early and middle pregnancy and provide useful genetic guidance for pregnancy and prenatal diagnosis. A total of 505 fetal specimens were collected and CNV sequencing (CNV-seq) analysis was performed to determine the types and clinical significance of CNVs, and relevant medical records were collected. The chromosomal abnormality rate was 54.3% (274/505), among which the numerical chromosomal abnormality rate was 40.0% (202/505) and structural chromosomal abnormality rate was 14.3% (72/505). Chromosomal monosomy mainly occurred on sex chromosomes, and chromosomal trisomy mainly occurred on chromosomes 16, 22, 21, 15, 13, and 9. The incidence of numerical chromosomal abnormalities in ≥35 year-old age pregnant women was significantly higher than <35 year-old age group. The highest incidence of pathogenic CNV (pCNV) was found in fetuses at ≤6 weeks of pregnancy (5.26%), and the incidence of variants of unknown significance (VOUS) CNVs decreased gradually with the increase of gestational age. The rate of chromosomal abnormalities of fetuses in early pregnancy (59.5%) was higher than that of fetuses in middle pregnancy (27.2%) (p < 0.001). There were 168 genes in VOUS + pCNV regions. 41 functions and 12 pathways (p < 0.05) were enriched of these genes by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Some meaningful genetic etiology information such as genes and pathways has been obtained, it may provide useful genetic guidance for pregnancy and prenatal diagnosis.

Etiology and outcome of non-immune hydrops fetalis in relation to gestational age at diagnosis and intrauterine treatment.

To determine the etiology and outcome of non-immune hydrops fetalis (NIHF) according to gestational age at diagnosis and intrauterine treatment. A total of 122 NIHF cases were included. Medical records and ultrasonographic images were reviewed. The etiology, outcome, and intrauterine treatment were assessed. The etiology was determined in 100 cases, and Hb Bart's disease was the most common. Two cases each of homozygous Southeast Asian ovalocytosis (SAO) and hemoglobin Constant Spring (Hb CS) were found. NIHF diagnosed in early gestation (<24 weeks) had a higher rate of chromosomal abnormalities and fetal demise. Intrauterine treatment was given in 18 cases, and 50% had successful live births. Hb Bart's disease was the most common cause of NIHF. SAO and Hb CS were associated with hydrops. NIHF in gestational age <24 weeks was associated with chromosomal abnormalities and fetal demise. Intrauterine treatment should be offered in selected cases.

Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number.

Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum—in the form of aluminum chloride (AlCl3) and at concentrations in the range of those measured in human tissues—incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis.

CLINICAL OUTCOMES AND SPERM QUALITY AFTER CHEMOTHERAPY IN PATIENTS WITH TESTICULAR CANCER

Testicular cancer survival rates have increased to 95%, leading to fatherhood becoming a major concern in half of male survivors. Since is not possible to predict how chemotherapy (CT) will affect spermatogenesis, sperm cryopreservation before cancer treatment is highly recommended. It is also unknown whether there is an increase in the rate of chromosomal or epigenetic abnormalities in post-CT sperm. Therefore, the use of fresh or stored sperm to undergo an IVF cycle is decided on an individual basis, based on the criteria of the attending doctor. Our aim was to evaluate the sperm quality and the IVF clinical outcomes of patients who had undergone CT to be cured of testicular cancer. This is a retrospective observational study including 119 patients diagnosed with testicular cancer who attended our clinic between 1998-2019 to cryopreserve semen before undergoing CT. A new sperm analysis was performed on the 38 patients that decided to return to our clinic after their cure. The total sperm concentration of the samples before and after CT was compared using paired t tests. Furthermore, the clinical IVF results obtained by the 27 patients who decided to undergo an IVF cycle were compared according to the origin of the sperm (frozen vs. fresh) with Fisher’s exact Tests. The patient’s mean age at the time of the cryopreservation was 31.67 ± 6.20 years. The spermiogram diagnosis at that moment was: normozoospermia (n=46, 38.65%), oligozoospermia (n=23, 19.33%), asthenozoospermia (n=13, 10.92%), oligoasthenozoospermia (n=26, 21.85%), cryptozooserpermia (n=5, 4.20%) and azoospermia (n=6, 5.04%). After cancer treatment, 38 patients (31.93%) returned to our clinic for a second semen analysis. The average time interval that elapsed was 4.26 ± 4.28 years. While 9 of the patients (23.68%) were azoospermic after CT treatment, 29 (76.32%) recovered spermatogenesis. Mean total sperm concentration before and after CT in those patients was 78.11 vs. 59.35 million, respectively (p>0.05). Twenty-seven patients underwent an IVF cycle. Following the doctor's instructions, 20 used frozen pre-CT samples, while 7 used fresh post-CT samples. Comparable ongoing pregnancy rates (66.66% vs. 56.75%; p>0.05), implantation rates (52.63% vs. 43.39%; p>0.05), miscarriage rates (0% vs. 14.28%; p>0.05) and live birth rates (100% vs. 90.47%; p>0.05) were found respectively. Acording to our data, the risk of azoospermia in patients diagnosed with testicular cancer undergoing CT is 24%. The patients who recover spermatogenesis after CT have a total sperm count similar to that before cancer treatment. Testicular cancer survivors obtain as good IVF clinical results as those obtained by the infertile population attending our clinic, whether they use a fresh sample or a sample that was frozen before the CT.

Prevalence of cytogenetic abnormalities and FMR1 gene premutation in a Portuguese population with premature ovarian insufficiency.

Chromosome abnormalities contribute to about 10% of cases of premature ovarian insufficiency. Most are associated with X chromosome. Fragile mental retardation 1 (FMR1) gene premutation has an estimated prevalence of 1% - 7% in sporadic cases and up to 13% in familial cases. Our aim was to describe the clinical characteristics, cytogenetic and FMR1 testing of a Portuguese population with premature ovarian insufficiency. Women diagnosed with premature ovarian insufficiency in a Portuguese tertiary centre were retrospectivelyanalysed. Data were retrieved from electronic medical records including clinical characteristics, cytogenetic and FMR1 testing. The main outcome measures were the prevalence of chromosome abnormalities and FMR1 premutation in a Portuguese population withpremature ovarian insufficiency. Ninety-four patients were included, with a median age at menopause of 36 years. The prevalence of chromosome abnormalities was 16.5% (14/85) and most were X chromosome related (78.6%). The prevalence of FMR1 premutation was 6.7% (6/90). The prevalence of karyotypic abnormalities or FMR1 premutation did not differ significantly between familial and sporadic cases. Neither chromosome abnormalities nor FMR1 premutation influenced age at menopause or follicle stimulating hormone levels at diagnosis in premature ovarian insufficiency patients. This is the first study describing the clinical characteristics and both cytogenetic and FMR1 testing in a Portuguese population with premature ovarian insufficiency. The rate of chromosome abnormalities in our sample was higher than in other populations, while the prevalence of FMR1 premutation was similar to previous reports. Our results underline the importance of genetic screening in premature ovarian insufficiency patients in both etiological study and genetic counselling.

Evaluations of Pregnancies Diagnosed with Fetal Neural Tube Defects in Our Center

Objective: To evaluate the risk factors, chromosomal abnormalities and additional anomalies of cases diagnosed with fetal neural tube defects (NTDs).&#x0D; Material and Method: The data of cases diagnosed with fetal NTDs between January 2016 and August 2020 with fetal NTD were retrieved from the hospital database. Only patients whose diagnosis confirmed after pregnancy termination and have a genetic test were included in the study. The family and antenatal history of patients included maternal age, maternal education level, diabetes mellitus, exposed to teratogenic drugs, smoking, and folic acid intake before or during the first trimester, siblings with a congenital abnormality, consanguinity, and AFP MOMs (alpha-fetoprotein, multiple of median) was obtained. Also, the type and level of NTDs and additional anomalies were noted. The data were evaluated using version 23.0 (SPSS Inc., Chicago, IL, USA).&#x0D; Results: During the study period, a total of 68 patients who met the study criteria were included in the study. A total of 27 patients diagnosed with spina bifida, 24 patients with anencephaly and 17 patients with encephalocele. The most anomalies resulted from NTDs was hydrocephaly and pes equinovarus. The most detected chromosomal abnormality was trisomy 13 (3 out of 7), and the most additional anomaly was the cleft lip and palate and detected in 4 (5.88%) patients. Pregestational DM was seen in 12/68 of pregnancies with fetal NTD.&#x0D; Conclusions&#x0D; The rate of additional anomalies and chromosomal abnormalities in cases diagnosed with fetal NTDs is high. Thus, a detailed ultrasonographic examination and genetic tests of fetuses with NTD is essential. The pregnancies complicated with pregestational DM have an increased risk for fetal NTD.

Copy number variation characterization and possible candidate genes in miscarriage and stillbirth by next-generation sequencing analysis.

BackgroundThe present study aimed to explore the etiological relationship between miscarriage and stillbirth and copy number variations (CNVs), as well as provide useful genetic guidance for high‐risk pregnancy.MethodsIn total, 659 fetal samples were recruited and subjected to DNA extraction and CNV sequencing (CNV‐seq), relevant medical records were collected.ResultsThere were 322 cases (48.86%) with chromosomal abnormalities, including 230 with numerical abnormalities and 92 with structural abnormalities. Chromosomal monosomy variations mainly occurred on sex chromosomes and trisomy variations mainly occurred on chromosomes 16, 22, 21, 18, 13 and 15. In total, 41 pathogenic CNVs (23 microdeletions and 18 microduplications) were detected in 27 fetal tissues. The rates of numerical chromosomal abnormalities were 29.30% (109/372), 32.39% (57/176) and 57.66% (64/111) in < 30‐year‐old, 30–34‐year‐old and ≥ 35‐year‐old age pregnant women, respectively, and increased with an increasing age (p < 0.001). There was statistically significant difference (χ2 = 7.595, p = 0.022) in the rates of structural chromosomal abnormalities in these groups (13.71%, 18.75% and 7.21%, respectively). The rates of numerical chromosomal abnormalities were 45.44% (219/482), 7.80% (11/141) and 0% (0/36) in the ≤ 13 gestational weeks, 14–27 weeks and ≥ 28 weeks groups, respectively, and decreased with respect to the increasing gestational age of the fetuses (p < 0.001).ConclusionsThe present study has obtained useful and accurate genetic etiology information that will provide useful genetic guidance for high‐risk pregnancies.

Trends of fetal chromosome analysis by amniocentesis before and after beginning of noninvasive prenatal testing: A single-center experience in Japan.

This study is to investigate the role of amniocentesis for prenatal diagnosis before and after the beginning of noninvasive prenatal testing (NIPT) in Japan. We performed a retrospective analysis of genetic amniocentesis at mid-trimester (15-20 gestational weeks) for fetal karyotype analysis at Nagoya City University between April 2006 and March 2020. The indications, test results, and the detection rate of fetal abnormal karyotype were compared before (phase 1, P1) and after (phase 2, P2) beginning of NIPT at April 2013. A total of 2458 (P1: 1132, P2: 1326) amniocentesis were enrolled in this study. The most frequent indication was advanced maternal age in both phases (P1: 78.2% %, P2: 81.1%). In P2, 110 patients (8.3%) received amniocentesis after positive or nonreportable NIPT results. Other indications were fetal abnormal findings by ultrasounds (P1: 15.4%, P2: 17.7%), abnormal maternal serum screening results (P1: 8.0%, P2: 10%), previous child with fetal chromosome aberration (P1: 6.5%, P2: 3.5%), and translocation of either partner (P1:1.5%, P2: 2.1%). The detection rate for fetal chromosomal aberrations including all indications was significantly increased in P2 (15.9%, 95% CI 14.0-18.0) as compared to P1 (9.0%, 7.4-10.8). However, if the indication was only advanced maternal age, the positive detection rate kept low in both phases (P1: 5.2%, 3.7-7.1, P2: 4.2%, 2.9-5.9). Since the initiation of NIPT, the detection rate of fetal chromosomal abnormalities was higher in this study, suggesting that amniocentesis cannot be strongly recommended for advanced maternal age alone.

P–224 Multinucleated and non-multinucleated embryos in PGT-A cycles: Is there any difference?

Abstract Study question Is multinucleation during cleavage stage correlated with the ploidy status of embryos and how does it affect the clinical outcome? Summary answer The presence of multinucleated embryos does not affect clinical outcome, although the risk of aneuploidy is higher in multinucleated embryos. What is known already Multinucleated blastomeres (ΜΝ) of cleavage stage embryos has been reported widely in scientific literature. Multinucleation has been associated with diminished embryo developmental competency and clinical outcomes such as lower implantation. Although this is an intriguing subject of research, it is not clear yet whether multinucleation is related to aneuploidy. Morphological irregularities such as multinucleation in blastomeres became a constant finding only after the perpetually evolving technology of time-lapse culture of embryos which in combination with PGT-A analysis, creates new research paths which aim to develop a new tool for selection or deselection of embryos for transfer. Study design, size, duration This retrospective study, included 97 PGT-A cycles, performed at Embryolab fertility clinic from May 2017 to December 2020, all cultured in time-lapse incubator (EmbryoScope). Two study groups were formed; the MN Group consisted of PGT-A cycles with at least one multinucleated embryo (n = 56) and the Control Group in which all PGT-A cycles had no multinucleated embryos (n = 38). Euploidy rate, type of chromosomal abnormality, cumulative pregnancy and live birth rates were compared between the two groups. Participants/materials, setting, methods Embryos were annotated for the existence of multinucleated blastomeres on Day 2 of their development. Biopsy was performed on Days 5/6 and embryos were genetically tested. One or two euploid embryos were transferred. Euploidy rate and clinical outcomes between the two groups were compared. Within the MN group, euploidy rate between multinucleated and non-multinucleated embryos was compared. For abnormal embryos, association of multinucleation with the type of abnormality was tested. SAS statistical analysis was performed. Main results and the role of chance Mean female age was 35.93 years in the MN group and 38.39 years in the control group. Blastocyst formation rate (expressed per fertilised oocytes) was similar between MN and Control group (74% vs 76%, p = 0.6303). In the MN group, 56 cases resulted in 44 embryo transfers while in the control group 38 cases resulted in 23 embryo transfers. Pregnancy rates (59.09% vs 65.21%, p = 0.6255) and clinical pregnancy rates (45.45% vs 39.13%, p = 0.4245) were not significantly different between MN and Control group. Initially, cumulative live birth rate was found to be significantly higher in the MN group compared to the Control group (62.96% vs 33.34%, p = 0.0417). However, when logistic and poisson regression was applied, it became obvious that this difference was not affected by multinucleation but from other factors such as female age. When comparing multinucleated and non-multinucleated embryos within the MN group, it was found that the mean number of euploid embryos was significantly higher in the non-multinucleated subgroup of embryos (p = 0.0021). No correlation was found between multinucleation and the type of chromosomal abnormality. Limitations, reasons for caution The sample size is the main limitation of the present study. More research with bigger sample size is needed in order to confirm the finding of the present study. Wider implications of the findings: The present study suggests that multinucleated blastomeres during embryo development is not an indication for diminished blastocyst formation and does not affect the clinical outcomes. However, within a sibling embryo population, non-multinucleated embryos tend to be euploid and this finding can be used to advance embryo selection efficiency. Trial registration number Not applicable

Cytogenetic analysis of early pregnancy loss after assisted reproduction treatment using intracytoplasmic sperm injection.

To evaluate the incidence of numerical chromosomal abnormalities in the patients with early pregnancy loss (EPL) following in vitro fertilization, and evaluate the role of different confounders of the risk of chromosomal abnormality-related pregnancy loss. A retrospective chart review of all patients from our in vitro fertilization (IVF) center who conceived using assisted reproduction techniques between April 2017 and 2019, who experienced a subsequent early pregnancy loss, and whose abortus materials were successfully karyotyped were included. Of the 243 patients experienced an early loss, the overall rate of chromosomal abnormality was 46.75%. The overall rate of aneuploidy in our patient group was 88.8% (64/72), whereas 6.94% (5/72) of the abnormal karyotypes were polyploid. The most common type of trisomy was Trisomy 16 (20.0%; 11/55) followed by Trisomy 15 (14.5%; 8/55). Univariate and multivariate analyses showed that maternal age (< 35 years) and the total number of retrieved oocytes per cycle (≥ 5) were risk factors for a chromosomal abnormality (< 0.001; < 0.05, respectively). The adjusted OR of karyotypic abnormalities was 0.45 for the antagonist cycle type (p < 0.05), and 0.58 for frozen embryo transfer (p < 0.05). Karyotypic abnormality is one of the main reasons for pregnancy loss following an IVF procedure. Although the pregnancy rates increased as a result of novel technologies, the ratio of EPL is still high. The implementation of preimplantation genetic screening techniques might lower the incidence of EPL due to chromosomal abnormalities, thus decreasing the burden on the physicians and the patients.

Genotoxic Effects of Radiofrequency-Electromagnetic Fields

Genotoxic Effects of Radiofrequency-Electromagnetic Fields

Follow-up in Patients With Non-invasive Prenatal Screening Failures: A Reflection on the Choice of Further Prenatal Diagnosis.

BackgroundOur aim was to provide a theoretical basis for clinicians to conduct genetic counseling and choose further prenatal diagnosis methods for pregnant women who failed non-invasive prenatal screening (NIPS).MethodsA retrospective analysis was performed on pregnant women who had failed NIPS tests.ResultsAmong the 123,291 samples, 394 pregnant women did not obtain valid results due to test failures. A total of 378 pregnant women were available for follow-up, while 16 patients were lost to follow-up. Of these 378, 135 pregnant women chose further prenatal diagnosis through amniocentesis, and one case of dysplasia was recalled for postpartum chromosome testing. The incidence rate of congenital chromosomal abnormalities in those who failed the NIPS was 3.97% (15/378), which was higher than that of the chromosomal abnormalities in the common population (1.8%). Among the pregnant women who received prenatal diagnosis, the positive rates of chromosomal abnormalities in the chromosomal microarray analysis/copy number variation sequencing (CMA/CNV-seq) group and in the karyotyping group were 15.28 and 4.76%, respectively.ConclusionPrenatal diagnosis should be strongly recommended in posttest genetic counseling for pregnant women with NIPS failures. Further, high-resolution detection methods should be recommended for additional prenatal diagnoses.